Topical benzoyl peroxide application on the
shoulder reduces Propionibacterium acnes: a
randomized study
Vendela Scheer, Malin Bergman, Maria Lerm, Lena Serrander and Anders Kalén
The self-archived postprint version of this journal article is available at Linköping University Institutional Repository (DiVA):
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Scheer, V., Bergman, M., Lerm, M., Serrander, L., Kalén, A., (2018), Topical benzoyl peroxide application on the shoulder reduces Propionibacterium acnes: a randomized study, Journal of
shoulder and elbow surgery, 27(6), 957-961. https://doi.org/10.1016/j.jse.2018.02.038
Original publication available at:
https://doi.org/10.1016/j.jse.2018.02.038
Copyright: Elsevier
Topical benzoyl peroxide application on the shoulder reduces Propionibacterium acnes; 1 a randomized study 2 3 Running head 4
P.acnes reduction with skin preparation 5
Authors 6
Vendela M Scheer Department of Clinical and Experimental Medicine, Linköping 7
University, Linköping, SE 581 85 Sweden, vendela.scheer@liu.se 8
Lena Serrander Division of Clinical Microbiology, Department of Clinical and 9
Experimental Medicine, Linköping University, Linköping, SE 581 85, Sweden 10
Maria Lerm Department of Clinical and Experimental Medicine, Linköping University; 11
Malin Berman Jungeström Divison of Clinical Microbiology, Faculty of Health Sciences, 12
University Hospital, Linköping, Sweden 13
Anders Kalen Division of orthopedics, Department of Clinical and Experimental Medicine 14
Faculty of Health Sciences at Linköping University, Linköping SE 581 85 Sweden 15
16
Acknowledgments: 17
Susanne Olivesjö for assisting during the study occasions 18
Johan Scheer for helping with the manuscript 19
Preoperative topical benzoyl peroxide of the shoulder reduces P.acnes and prevents 1
recolonization, compared to chlorhexidine soap. 2
3
Abstract 4
Background: Propionibacterium acnes (P.acnes) is a common cause of infection following 5
shoulder surgery. Studies have shown that standard surgical preparation does not eradicate 6
P.acnes. The purpose of this study was to examine if topical application with benzoyl
7
peroxide gel (BPO) could decrease the presence of P.acnes, compared to the today’s standard 8
treatment with chlorhexidine soap (CHS). We also investigated and compared the 9
recolonization of the skin after surgical preparation and draping, between the BPO- and CHS-10
treated groups. 11
Methods: A single blinded non-surgical study with forty volunteers – twenty-four men and 12
sixteen women were randomized to preoperative topical treatment at home with either 5 % 13
BPO or 4 % CHS in the area of a deltopectoral approach of their left shoulder. Four skin 14
swabs from the area were taken in a standardized manner at different times: Before and after 15
topical treatment, after surgical skin preparation and sterile draping and 120 minutes after 16
draping. 17
Results: Topical treatment with BPO significantly reduced the presence of P.acnes as CFU 18
on the skin after surgical preparation. P.acnes was found in 1/20 subjects of the BPO group, 19
and 7/20 in the CHS-group (p<0.044). The results remained after two hours (p<0.048). 20
Conclusion: Topical preparation with BPO before shoulder surgery may be effective in 21
reducing P.acnes on the skin and prevent recolonization. 22
Level of evidence: Level II 26
Introduction 27
28
Propionibacterium acnes (P.acnes) is a gram-positive facultative anaerobic rod, a human 29
commensal bacteria who resides in the pilosebaceous ducts of the skin 1, 6. The reported 30
numbers of shoulder infections after surgery caused by P. acnes is increasing and so is the 31
incidence of resistance to antibiotics 1, 3, 11, 16, 21, 26. The ability of P.acnes to create biofilm 32
causes severe infections that may involve reoperation and long-term antibiotic treatment. To 33
decrease the bacterial burden on the skin before operation one strategy is topical preparation 34
at home with chlorhexidine soap (CHS). Despite strict preoperative preparation with 35
chlorhexidine solution in 70 % ethanol earlier studies has shown that chlorhexidine is not 36
able to eradicate P.acnes from the skin. From 7% up to 50 % of P.acnes may still be present 37
on the skin 10, 15, 23, 25. Benzoyl peroxide (BPO) is widely used as topical therapy for acne 38
vulgaris, and has so been for more than five decades. The bactericidal effect of BPO on 39
P.acnes is well documented, and has not been associated with the development of P.acnes
40
resistance. 4, 8, 12, 17. The purpose of this study was to examine if topical application with BPO 41
could decrease the presence of P.acnes on the treated skin, compared to the today’s standard 42
treatment with CHS. We also investigated and compared the recolonization of the skin after 43
surgical preparation and draping, between the BPO- and CHS-treated groups. 44
45 46 47
Material and Methods 48
49
A single-blinded non-surgical randomized study, with forty healthy volunteers in aged from 50
20 to 66, twenty-four men and sixteen women gave informed consent to participate. 51
Exclusion criteria were antibiotic treatment 10 days prior to trial day, presence of diabetes 52
mellitus, local skin lesions and local or systemic corticoid steroid treatment. Participants were 53
randomized in blocks of four to CHS or BPO-pretreatment. The investigator was blinded to 54
allocated treatment. One week prior to the trial day the participants received verbal and 55
written instructions. Thereafter the first skin swab was collected on the left shoulder (Sample 56
A). 57
58
The groups prepared as follows: 59
1. BPO group 60
The treatment set up in the BPO-group was designed in collaboration with a 61
dermatologist, who advised on drug concentration and application frequency to 62
minimize local side effects, e.g. erythema, peeling and dryness. Hence the BPO group 63
started the procedure 48 hours before the trial day. After showering and drying they 64
applied a 5 cm strip of 5 % BPO on the left shoulder. They repeated the application 65
the following morning and evening. The fifth and last time was the morning on trial 66 day. 67 68 2. CHS group 69 70
According to the local routine protocol the CHS group prepared with 4% 71
chlorhexidine soap on their left shoulder, starting the day before the trial day with two 72
showers, with a minimum of two hours in between, using two sponges each, and on 73
trial day one shower in the morning with two more sponges. 74
75
A treatment diary was administered to each participant for affirmation of each gel application 76
or shower, showing 100 % compliance. On each trial day occasion four volunteers were 77
placed on separate beds in the same operating room with laminar airflow (LAF) with their 78
upper body inside the LAF-circle. Before surgical preparation the next skin swab was 79
collected from the left treated side (Sample B). At the same time a control swab was taken 80
from the contralateral shoulder. A skin swab was collected after the treated left side was 81
prepared for 2 minutes with 0.5% chlorhexidine solution in 70% ethanol, and sterile drape 82
was applied (Sample C). 120 minutes after surgical preparation and sterile draping the last 83
skin swab was collected (Sample D) (Table 1). All skin swabs were taken by rub 15 times 84
over a 10 cm deltopectoral interval, and immediately put into the medium. Within thirty 85
minutes the skin swabs were transported to the laboratory, vortexed for 10 sec before cultured 86
on anaerobic blood agar medium without antibiotics and placed in an anaerobic incubator. 87
After five days in the incubator the number of colony forming units (CFU) were counted and 88
divided into five groups according to the numbers of CFUs (Table 2).The bacterial colonies 89
were classified on agar plates by surface characteristics. P.acnes was identified with matrix-90
assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry. 91
Analyzes were blinded and performed by the main author. Code was broken after analyzes 92
were done. 93
94 95
Statistical Analysis 96
97
For dichotomous variables we used Fischer´s exact test and otherwise Chi-squared test. P-98
values <0.05 was considered being statistically significant. 99
Results 101
102
Before any treatment (sample A), P.acnes was detected in 38/40 subjects, and there was no 103
significant difference in CFU between the groups. In the BPO- group, presence of P.acnes 104
diminished with treatment (Figure 1a) but not in the CHS-group (Figure 1b). After skin 105
preparation (Sample C) we could detect CFU of P. acnes in only 1/20 in the BPO-group 106
compared to 7/20 in the CHS-group (p=0.044, Figure 2). Two hours later, the BPO-group 107
showed a significantly lower P.acnes presence than the CHS-group (p=0.048, Figure 2). 108
There was no significant difference in presence of P.acnes before surgical field preparation 109
(Sample B) and after two hours (Sample D) in the CHS-group (Figure 1b), in contrast to the 110
BPO-group (Figure 1a). 111
112
The total number of CFU (which might comprise of more bacterial strains than P.acnes) also 113
diminished after topical BPO-treatment (p-value 0.035) but not in the CHS-treated group 114
(p=0.284). 115
116 117
Discussion 118
119
To the authors knowledge this is the first randomized study which compares topical BPO-120
treatment to topical CHS-treatment as preoperative preparations. We show that BPO-121
treatment significantly decreases the presence of P.acnes after preoperative preparation and 122
the result remains after 120 minutes. To our knowledge only one other study have 123
investigated the effect of BPO-treatment on shoulders undergoing surgery and presented a 124
reduction of P.acnes compared to the untreated contralateral shoulder 24. It is well-known that 125
chlorhexidine does not eradicate P.acnes on the skin after surgical preparation 5, 10, 25, which 126
is in concordance with present study. 127
128
We detected a very high proportion of detected P.acnes both at the investigated shoulder 129
(38/40) as well as in the control shoulder (37/40). In other studies on shoulders this detection 130
varies between 42-76% 7, 18, 23. The fact that we used healthy volunteers is hardly a sufficient 131
explanation. Neither gender nor age appear to differ compared to earlier studies. A more 132
likely explanation is the method used. Factors that might effect the results are the swabbed 133
area, the pressure applied on the swab, duration and frequency, which may make comparisons 134
difficult. Skin – treated or even untreated - can be difficult to culture P.acnes from, because 135
of its preference to grow deep into the skin. Therefore, prior to this study, we performed a 136
small pilot study where we compared different methods. The pilot study resulted in the 137
choice of procedure with skin- swab that we used in the present study. 138
139
It is sometimes stated that P.acnes is more prevalent in men 5, 13, 19 something that was not 140
confirmed in our study. This statement may reside on the indirect observation that deep 141
postoperative infection with P.acnes is more often found in the male population 26, 29, 142
whereas other studies using swabs show no gender difference 18, 23 143
144
Dermatological studies indicate that the rapid effect of BPO 4, 14 makes a two day preparation 145
sufficient in reducing P.acnes also minimizing side effect such as redness, dry and scaly skin. 146
These side effects appear in the beginning 14, 27 of treatment and may be a drawback in 147
general treatment with BPO in conjunction with shoulder surgery. 148
149
Interestingly there was no difference in the prevalence of P.acnes in the CHS- group before 150
skin preparation until the swab taken after two hours (Figure 1b), while there was a 151
significant reduction in the BPO-group (Figure 1a). Since a risk factor for surgical site 152
infection is duration of surgery 2, 22, 28, it appears troublesome that the surgical field has the 153
same amount of P.acnes as an unprepared shoulder. 154
155
To decrease confounding by external bacterial seeding, it must be emphasized that the 156
sampling was performed under as surgery like conditions as possible in an operation room 157
with state-of-the-art laminar air flow and sterile draping. Also subject compliance to assigned 158
treatment was 100%. 159
160
There are limitations to our study. Using healthy volunteers may not reflect the anticipated 161
response to BPO in patients – presumably older and with co-morbidities - undergoing 162
shoulder surgery. These may have a different bacterial flora and response to BPO. 163
Furthermore one may anticipate that there is a correlation between P. acnes on the skin from 164
differences in the CHS-group, but our findings on this subject are consistent with those of 167
other studies 9, 15, 20, 23, 25. Quantification of colonizing bacteria on the skin pre-operatively has 168
often been used as a marker for risk of post-operative infection, but how well it really 169
corresponds to risk for infections for different bacterial species is not so well studied. 170
171 172
Conclusion 173
In summary, this non-surgical case study, shows that there is a significant difference between 174
the BPO and CHS group immediately after surgical preparation and that the results remained 175
after 120 minutes. The skin swabs give micro biotic data of the skin, if that has any 176
correlation to SSI we do not know. The most likely explanation is that BPO affects the re-177
emergence of P.acnes from deeper layers and thereby decreases recolonization of the skin. 178
Given this evidence for the effect of BPO on the skin after surgical preparation and over time, 179
topical preparation with BPO before shoulder surgery may be effective in reducing P.acnes 180
on the skin and prevent recolonization. 181
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Figure legends 270
271
Figure 1. Skin swabs were analyzed from the treated left shoulder and presence of P.acnes 272
(yes or no) was detected. 1a: BPO-group (n=20). 1b: CHS-group (n=20). Time of sampling, 273 see Table 1. 274 *statistically significant. 275 276
Figure 2 Skin swabs were analyzed from left shoulder and presence of P.acnes (yes or no) 277
was detected in BPO –treated group n = 20, compared with CHS-treated group, n = 20. Time 278
of sampling, see Table 1. 279
*statistically significant. 280
281 282
Sa mp le A Sa mp le B Sa mp le C Sa mp le D 0 5 1 0 1 5 2 0 1 a . B P O g r o u p p = 0 . 0 4 4 * p = 0 . 3 4 2 p = 0 . 0 1 * N o o f s u b je c ts Sa mp le A Sa mp le B Sa mp le C Sa mp le D 0 5 1 0 1 5 2 0 1 b . C H S g r o u p p = 0 . 3 4 2 p = 0 . 3 4 1 p = 0 , 1 7 6 N o o f s u b je c ts
BP O S am ple C CH S S am ple C BP O S am ple D CH S S am ple D 0 5 1 0 p = 0 . 0 4 4 * N o o f s u b je
Table 1. Flow chart of skin swab
Sample Time
A Before treatment, one week before trial day B Trial day, after topical treatment at home C After surgical preparation and sterile draping D 120 min after surgical preparation and sterile drape Control Trial day, right shoulder, not treated
Group 0 1 2 3 4
